Nonvalvular atrial fibrillation (AF) is an age-related public health problem associated with marked morbidity and mortality. We propose to prospectively examine the structural, hemodynamic, and neurohormonal/ inflammatory factors associated with first AF and investigate whether sleep apnea independently predicts AF. In Aim 1, we will confirm that diastolic function and left atrial (LA) volume are predictive of AF, incremental to clinical and other echocardiographic variables. We hypothesize that diastolic dysfunction and increased LA volume independently predict nonvalvular AF. In Aim 2, the distribution and correlates of changes in diastolic function and LA volume will be described, and we will determine whether serial measurements of these parameters provide incremental information on risk of AF. In Aim 3, we plan to explore how neurohormonal activation, specifically atrial natriuretic peptide (ANP) release, and the inflammatory marker, C-reactive protein (CRP), are associated with LA size, diastolic function, and AF development. We hypothesize that there is an independent role for ANP, but not for CRP, in the prediction of AF, after clinical and echocardiographic parameters have been considered. In Aim 4, we will assess relationships between arterial stiffness, diastolic function and LA volume, and determine whether arterial stiffness independently predicts AF. In Aim 5, we will evaluate sleep apnea as an independent predictor of AF development, after accounting for other clinical and echocardiographic risk factors. We plan to recruit 800 adults at significant risk for nonvalvular AF on the basis of age > 65 years and the presence of two or more known AF risk factors (hypertension, diabetes, history of coronary artery disease, and history of congestive heart failure). Prior history of AF, embolic stroke, organic valvular disease and congenital heart disease are the major exclusion criteria. All participants must be able to provide informed consent. Echocardiography, electrocardiogram (ECG), ANP, CRP, noninvasive arterial stiffness assessments (pulse wave velocity and augmentation index) will be obtained at baseline and annually thereafter. The Berlin Sleep Questionnaire to assess risk of sleep apnea will be completed by all participants at baseline and annually. A subgroup of 200 participants will undergo sleep studies, using a portable recording system, for detection of sleep apnea. Ascertainment of AF involves regular ECG surveillance, and patient report of AF with ECG confirmation. Identification of the cascade of factors contributing to AF development will have important implications in primary prevention of this major public health problem.